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991.
992.
Henry Ofosuhene Sintim Toru Tashiro Naoki Motoyama 《Archives of insect biochemistry and physiology》2012,81(3):148-159
Three diverse insects, a polyphagous “leaf chewer” (Atractomorpha lata), a polyphagous “sap feeder” (Myzus persicae), and a “restrictive feeder” (Plutella xylostella) responded differently when fed with eight cultivars of sesame either as whole leaf or via artificial diet. There was limited or no correlation in induction between detoxifying enzyme substrates (esterase, glutathione s‐transferase [GST], and mixed function oxidase [MFO] activities) when activity toward various substrates α‐naphthyl acetate, 1‐chloro‐2,4‐dinitrobenzene, 1,2‐dichloro‐4‐nitrobenzene, and p‐nitroanisole (pNA), were compared although they were generally elevated in the tissues from insects on sesame than a reference fed with radish seedlings. In A. lata, esterase activity for the cultivar 11Pusan and 45Laos were three‐fold higher compared to the reference, while other cultivars, 24Nanbu‐twasaki and 56S‐radiatum were—two‐ to three‐fold lower than the reference. In M. persicae, the esterase activity was as much as five‐fold higher than the reference in one test cultivar. GST activities of the sesame cultivars were generally higher (≈two‐fold) than the reference in all insects and at variable ratios among the cultivars. The MFO activity toward pNA in grasshoppers feeding on these sesame cultivars was either highly expressed or nonexistent. These results indicate that although the cultivars belong to the same species, they might have undergone changes in secondary phytochemicals in response to varying biogeographical distribution. Each insect species is suspected to target a specific plant chemical burden that it tries to overcome in each cultivar through enzyme activation. 相似文献
993.
Cash JN Angerman EB Keutmann HT Thompson TB 《Molecular endocrinology (Baltimore, Md.)》2012,26(7):1167-1178
Follistatin (FST)-type proteins are important antagonists of some members of the large TGF-β family of cytokines. These include myostatin, an important negative regulator of muscle growth, and the closely related activin A, which is involved in many physiological functions, including maintenance of a normal reproductive axis. FST-type proteins, including FST and FST-like 3 (FSTL3), differentially inhibit various TGF-β family ligands by binding each ligand with two FST-type molecules. In this study, we sought to examine features that are important for ligand antagonism by FST-type proteins. Previous work has shown that a modified construct consisting of the FST N-terminal domain (ND) followed by two repeating follistatin domains (FSD), herein called FST ND-FSD1-FSD1, exhibits strong specificity for myostatin over activin A. Using cell-based assays, we show that FST ND-FSD1-FSD1 is unique in its specificity for myostatin as compared with similar constructs containing domains from FSTL3 and that the ND is critical to its activity. Furthermore, we demonstrate that FSD3 of FST provides affinity to ligand inhibition and confers resistance to perturbations in the ND and FSD2, likely through the interaction of FSD3 of one FST molecule with the ND of the other FST molecule. Additionally, our data suggest that this contact provides cooperativity to ligand antagonism. Cross-linking studies show that this interaction also potentiates formation of 1:2 ligand-FST complexes, whereas lack of FSD3 allows formation of 1:1 complexes. Altogether, these studies support that domain differences generate FST-type molecules that are each uniquely suited ligand antagonists. 相似文献
994.
Janovick JA Pogozheva ID Mosberg HI Cornea A Conn PM 《Molecular endocrinology (Baltimore, Md.)》2012,26(7):1179-1188
G protein-coupled receptors (GPCR) play central roles in almost all physiological functions, and mutations in GPCR are responsible for over 30 hereditary diseases associated with loss or gain of receptor function. Gain of function mutants are frequently described as having constitutive activity (CA), that is, they activate effectors in the absence of agonist occupancy. Although many GPCR have mutants with CA, the GnRH receptor (GnRHR) was not, until 2010, associated with any CA mutants. The explanation for the failure to observe CA appears to be that the quality control system of the cell recognizes CA mutants of GnRHR as misfolded and retains them in the endoplasmic reticulum. In the present study, we identified several human (h)GnRHR mutants with substitutions in transmembrane helix 6 (F(272)K, F(272)Q, Y(284)F, C(279)A, and C(279)S) that demonstrate varying levels of CA after being rescued by pharmacoperones from different chemical classes and/or deletion of residue K(191), a modification that increases trafficking to the plasma membrane. The movement of the mutants from the endoplasmic reticulum (unrescued) to the plasma membrane (after rescue) is supported by confocal microscopy. Judging from the receptor-stimulated inositol phosphate production, mutants F(272)K and F(272)Q, after rescue, display the largest level of CA, an amount that is comparable with agonist-stimulated activation. Because mutations in other GPCR are, like the hGnRHR, scrutinized by the quality control system, this general approach may reveal CA in receptor mutants from other systems. A computer model of the hGnRHR and these mutants was used to evaluate the conformation associated with CA. 相似文献
995.
Bonnart C Gérus M Hoareau-Aveilla C Kiss T Caizergues-Ferrer M Henry Y Henras AK 《Nucleic acids research》2012,40(13):6270-6289
Ribosome production, one of the most energy-consuming biosynthetic activities in living cells, is adjusted to growth conditions and coordinated with the cell cycle. Connections between ribosome synthesis and cell cycle progression have been described, but the underlying mechanisms remain only partially understood. The human HCA66 protein was recently characterized as a component of the centrosome, the major microtubule-organizing center (MTOC) in mammalian cells, and was shown to be required for centriole duplication and assembly of the mitotic spindle. We show here that HCA66 is also required for nucleolar steps of the maturation of the 40S ribosomal subunit and therefore displays a dual function. Overexpression of a dominant negative version of HCA66, accumulating at the centrosome but absent from the nucleoli, alters centrosome function but has no effect on pre-rRNA processing, suggesting that HCA66 acts independently in each process. In yeast and HeLa cells, depletion of MTOC components does not impair ribosome synthesis. Hence our results suggest that both in yeast and human cells, assembly of a functional MTOC and ribosome synthesis are not closely connected processes. 相似文献
996.
Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation 总被引:1,自引:0,他引:1
997.
998.
Alexander A. Shestov Julien Valette Dinesh K. Deelchand Kamil U?urbil Pierre-Gilles Henry 《Neurochemical research》2012,37(11):2388-2401
Metabolic modeling of dynamic 13C labeling curves during infusion of 13C-labeled substrates allows quantitative measurements of metabolic rates in vivo. However metabolic modeling studies performed in the brain to date have only modeled time courses of total isotopic enrichment at individual carbon positions (positional enrichments), not taking advantage of the additional dynamic 13C isotopomer information available from fine-structure multiplets in 13C spectra. Here we introduce a new 13C metabolic modeling approach using the concept of bonded cumulative isotopomers, or bonded cumomers. The direct relationship between bonded cumomers and 13C multiplets enables fitting of the dynamic multiplet data. The potential of this new approach is demonstrated using Monte-Carlo simulations with a brain two-compartment neuronal-glial model. The precision of positional and cumomer approaches are compared for two different metabolic models (with and without glutamine dilution) and for different infusion protocols ([1,6-13C2]glucose, [1,2-13C2]acetate, and double infusion [1,6-13C2]glucose?+?[1,2-13C2]acetate). In all cases, the bonded cumomer approach gives better precision than the positional approach. In addition, of the three different infusion protocols considered here, the double infusion protocol combined with dynamic bonded cumomer modeling appears the most robust for precise determination of all fluxes in the model. The concepts and simulations introduced in the present study set the foundation for taking full advantage of the available dynamic 13C multiplet data in metabolic modeling. 相似文献
999.
Rullo J Becker H Hyduk SJ Wong JC Digby G Arora PD Cano AP Hartwig J McCulloch CA Cybulsky MI 《The Journal of cell biology》2012,197(1):115-129
Leukocytes arrested on inflamed endothelium via integrins are subjected to force imparted by flowing blood. How leukocytes respond to this force and resist detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937 cells revealed that force triggers actin polymerization at upstream α4β1 integrin adhesion sites and the adjacent cortical cytoskeleton. Scanning electron microscopy revealed that this culminates in the formation of structures that anchor monocyte adhesion. Inhibition of actin polymerization resulted in cell deformation, displacement, and detachment. Transfection of dominant-negative constructs and inhibition of function or expression revealed key signaling steps required for upstream actin polymerization and adhesion stabilization. These included activation of Rap1, phosphoinositide 3-kinase γ isoform, and Rac but not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces. 相似文献
1000.
The p53 circuit board 总被引:1,自引:0,他引:1
Sullivan KD Gallant-Behm CL Henry RE Fraikin JL Espinosa JM 《Biochimica et biophysica acta》2012,1825(2):229-244